Early intraoperative iron-binding proteins are associated with acute kidney injury after cardiac surgery Nora Choi, MSc, Reid Whitlock, BSc, Jessica.

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Early intraoperative iron-binding proteins are associated with acute kidney injury after cardiac surgery Nora Choi, MSc, Reid Whitlock, BSc, Jessica Klassen, MD, Michael Zappitelli, MD, Rakesh C. Arora, MD, Claudio Rigatto, MD, Julie Ho, MD The Journal of Thoracic and Cardiovascular Surgery Volume 157, Issue 1, Pages 287-297.e2 (January 2019) DOI: 10.1016/j.jtcvs.2018.06.091 Copyright © 2018 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Prospective observational cohort of adult patients undergoing cardiac surgery, n = 301. AKI, Acute kidney injury; Cr, creatinine; KDIGO, Kidney Disease Improving Global Outcomes. The Journal of Thoracic and Cardiovascular Surgery 2019 157, 287-297.e2DOI: (10.1016/j.jtcvs.2018.06.091) Copyright © 2018 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Intraoperative serum ferritin and transferrin saturation in patients with AKI versus without AKI at the start of CPB and 1 hour on CPB. Lower serum ferritin was associated with those with AKI at (A) start of CPB (P = .005) and (B) 1-hour CPB (P = .001). No difference in transferrin saturation between patients with AKI and patients without AKI at both start of CPB and 1-hour CPB. P = .19 (C) and P = .59 (D). Box plots demonstrate horizontal median line between 25th and 75th percentiles. The upper and lower whiskers represent the minimum and maximum values of nonoutliers, and dots represent outliers. CPB, Cardiopulmonary bypass. The Journal of Thoracic and Cardiovascular Surgery 2019 157, 287-297.e2DOI: (10.1016/j.jtcvs.2018.06.091) Copyright © 2018 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Phases of renal IRI during cardiac surgery with a proposed model for the role of iron-binding proteins. Intraoperative catalytic free iron release during IRI on CPB may cause renal tubular cell lipid peroxidation, which can lead to ferroptosis, a novel iron-dependent form of cell death in renal IRI/AKI (middle). Early intraoperative iron-binding proteins and postoperative iron-sequestering proteins may be endogenous renoprotective strategies that act to mitigate the impact of catalytic free iron release during CPB (top). The importance of maintaining iron homeostasis during cardiac surgery highlights the potential for minimally invasive, intraoperative AKI prevention strategies, and novel AKI therapeutics targeting these pathways (bottom). NGAL, Neutrophil gelatinase-associated lipocalin; IRI, ischemia–reperfusion injury; CPB, cardiopulmonary bypass; AKI, acute kidney injury. The Journal of Thoracic and Cardiovascular Surgery 2019 157, 287-297.e2DOI: (10.1016/j.jtcvs.2018.06.091) Copyright © 2018 The American Association for Thoracic Surgery Terms and Conditions

Proposed role of iron-binding proteins during cardiac surgery–related renal IRI and AKI. The Journal of Thoracic and Cardiovascular Surgery 2019 157, 287-297.e2DOI: (10.1016/j.jtcvs.2018.06.091) Copyright © 2018 The American Association for Thoracic Surgery Terms and Conditions

Video 1 Intraoperative iron-binding proteins are associated with the development of postcardiac surgery AKI. Video available at: https://www.jtcvs.org/article/S0022-5223(18)32021-X/fulltext. The Journal of Thoracic and Cardiovascular Surgery 2019 157, 287-297.e2DOI: (10.1016/j.jtcvs.2018.06.091) Copyright © 2018 The American Association for Thoracic Surgery Terms and Conditions